Interferon- release assays in tuberculosis contacts: is there a window period?

Abstract

The tuberculin skin test (TST) is the established procedure for diagnosis of latent tuberculosis infection (LTBI) among the contacts of an infectious tuberculosis (TB) case. TST may convert to positive ≤8 weeks after Mycobacterium tuberculosis infection, an interval that is usually referred to as the “window period”. A negative TST obtained <8 weeks before does not exclude infection, and a second test is recommended 1, 2. However, TST has some limitations, such as cross-reactivity with Bacille Calmette–Guerin (BCG) and with nontubercular mycobacterial infections. T-cell interferon-γ release assays (IGRA) are emerging as new screening tools for LTBI diagnosis. IGRAs incorporate specific antigens of M. tuberculosis that are absent in BCG strains and in the majority of nontubercular mycobacteria, offering enhanced specificity for detecting M. tuberculosis infection 3. In addition, their use has been approved for screening of infection in contacts 1, 4. Most TB contact studies have shown a better correlation of IGRA with the intensity of M. tuberculosis exposure than that obtained using TST, particularly in patients previously vaccinated with BCG 5. Yet, to our knowledge, no study has considered carefully the window period after M. tuberculosis exposure while simultaneously evaluating responses for TST and IGRA. The aim of this study was to find out which of the two tests converts earlier to positive in persons with recent infection after contact with an infectious TB case. We used a longitudinal prospective analysis to study 184 healthy adults, all having had recent contact with a microbiologically confirmed pulmonary TB index patient. The setting was a specialized TB clinic in Pontevedra, Spain, where the incidence of TB has historically been among the highest in Western …